Chrysin, a natural flavone, improves murine inflammatory bowel diseases

Shin, Eun Jung; Kwon, Hyuck-Se; Kim, Yoon Hee; Shin, Hyun‐Kyung; Kim, Jin‐Kyung

doi:10.1016/j.bbrc.2009.02.071

Cited by 100 publications

(57 citation statements)

References 33 publications

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“…A previous study indicated that chrysin activates human PXR and induces UGT1A1 promoter in a cell-based reporter assay (Shin et al, 2009). We hypothesized that chrysin could also activate mouse PXR and induce Cyp3a11 promoter.…”

Section: Resultsmentioning

confidence: 90%

“…A previous study demonstrated the therapeutic effect of chrysin on DSS-induced IBD (Shin et al, 2009). To assess whether chrysin would also provide protection to the same IBD model, we added dextran sulfate sodium (MW 36000-50000; MP Biomedicals) to the drinking water to induce the acute colitis in mice.…”

Section: Resultsmentioning

confidence: 99%

“…A recent investigation suggested that chrysin coadministration ameliorated inflammatory symptoms in a mouse model of DSS-induced colitis and blocked NF-kB activation in intestinal epithelial IEC-6 cells (Shin et al, 2009). In the past, chrysin was demonstrated to be a human PXR ligand in vitro (Sugatani et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Chrysin Ameliorates Chemically Induced Colitis in the Mouse through Modulation of a PXR/NF-κB Signaling Pathway

Dou

Zhang

et al. 2013

J Pharmacol Exp Ther

101

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Targeted activation of pregnane X receptor (PXR) in recent years has become a therapeutic strategy for inflammatory bowel disease. Chrysin is a naturally occurring flavonoid with antiinflammation activity. The current study investigated the role of chrysin as a putative mouse PXR agonist in preventing experimental colitis. Pre-administration of chrysin ameliorated inflammatory symptoms in mouse models of colitis (dextran sodium sulfate-and 2,4,6-trinitrobenzene sulfonic acid-induced) and resulted in down-regulation of nuclear transcription factor kB (NF-kB) target genes (inducible NO synthase, intercellular adhesion molecule-1, monocyte chemotactic protein-1, cyclooxygenase 2, tumor necrosis factor-a, and interleukin 6) in the colon mucosa. Chrysin inhibited the phosphorylation/degradation of inhibitor kBa (IkBa), which correlated with the decrease in the activity of myeloperoxidase and the levels of tumor necrosis factor-a and interleukin 6 in the colon. Consistent with the in vivo results, chrysin blocked lipopolysaccharide -stimulated nuclear translocation of NF-kB p65 in mouse macrophage RAW264.7. Furthermore, chrysin dose-dependently activated human/mouse PXR in reporter gene assays and up-regulated xenobiotic detoxification genes in the colon mucosa, but not in the liver. Silencing of PXR by RNA interference demonstrated necessity of PXR in mediating chrysin's ability to induce xenobiotic detoxification genes and NF-kB inactivation. The repression of NF-kB transcription activity by chrysin was confirmed by in vitro PXR transduction. These findings suggest that the effect of chrysin in preventing chemically induced colitis is mediated in large part by a PXR/NF-kB pathway. The data also suggest that chrysin or chrysin-like flavonoids could be further developed as intestine-specific PXR activators.

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Section: Resultsmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Chrysin Ameliorates Chemically Induced Colitis in the Mouse through Modulation of a PXR/NF-κB Signaling Pathway

Dou

Zhang

et al. 2013

J Pharmacol Exp Ther

101

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“…The use of medicinal plants or their active components is becoming an increasingly attractive approach for the management of IBD (Shin et al, 2009;Zhang et al, 2014). In the present study, as a part of our ongoing screening program to evaluate the antiinflammatory potentials of natural compounds (Dou et al, 2013a;Zhang et al, 2014), we investigated the anti-inflammatory effects of R1 on DSS-or TNBS-induced colitis.…”

Section: Discussionmentioning

confidence: 99%

Notoginsenoside R1 Attenuates Experimental Inflammatory Bowel Disease via Pregnane X Receptor Activation

Zhang

Ding

Wang

et al. 2014

J Pharmacol Exp Ther

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Notoginsenoside R1 (R1) is the main bioactive component in Panax notoginseng, an old herb medicine widely used in Asian countries in the treatment of microcirculatory diseases. However, little is known about the effect of R1 on inflammatory bowel disease (IBD). The present study demonstrated that R1 alleviated the severity of dextran sulfate sodium-induced colitis in mice by decreasing the activity of myeloperoxidase, the production of cytokines, the expression of proinflammatory genes, and the phosphorylation of IkB kinase, IkBa, and p65 in the colon. Further studies indicated that R1 dose-dependently activated human/mouse pregnane X receptor (PXR), a known target for decreasing inflammation in IBD, and upregulated the expression of genes involved in xenobiotic metabolism in colorectal cells and the colon. Ligand pocket-filling mutant (S247W/C284W or S247W/ C284W/S208W) of the human PXR abrogated the effect of R1 on PXR activation. Time-resolved fluorescence resonance energy transfer PXR competitive binding assay confirmed R1 (ligand) binding affinity. In addition, PXR overexpression inhibited nuclear factor-kB (NF-kB)-luciferase activity, which was potentiated by R1 treatment. PXR knockdown by small interfering RNA demonstrated the necessity of PXR in R1-induced upregulation of the expression of xenobiotic-metabolizing enzymes and downregulation of NF-kB activity. Finally, the anti-inflammatory effect of R1 was confirmed in trinitrobenzene sulfonic acid-induced colitis in mice. These findings suggest that R1 attenuates experimental IBD possibly via the activation of intestinal PXR signaling.

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“…Chrysin (5,7-dihydroxyflavone, ChR), a natural flavonoid present in our daily diet, has recently been shown to be a potent inhibitor of the enzyme aromatase (2). ChR also has anti-inflammatory (3,4), and antioxidant (5) effects, and has been found to possess the ability to inhibit growth and induce apoptosis in a variety of human cancer cells, including cervical cancer (6), leukemia (7,8), colon carcinoma (9), esophageal adenocarcinoma (10) and lung adenocarcinoma cells (11). Nevertheless, poor oral bioavailability has been a major limitation for the successful use of dietary flavonoids as cancer chemotherapeutic agents (12,13).…”

Section: Introductionmentioning

confidence: 99%

Induction of apoptosis by 5,7-dihydroxy-8-nitrochrysin in breast cancer cells: The role of reactive oxygen species and Akt

Zhao

Tian²,

Cao³

et al. 2010

Int J Oncol

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Abstract. 5,7-dihydroxy-8-nitrochrysin (NOC), a novel synthetic chrysin analogue, induces apoptosis in human cancer cells. We previously demonstrated that NOC possesses stronger cytotoxicity towards human colon carcinoma and human gastric carcinoma cells than chrysin. Herein, we demonstrate the mechanism by which NOC preferentially suppresses the viability of the MDA-MB-453 human breast cancer cell line (ER negative, Her2 overexpressing) and moderately suppresses the viability of the MCF-7 cell line (ER positive, Her2 low), but has little effect on the immortalized non-cancerous HBL-100 breast cell line (ER positive, Her2 low). Moreover, the results of our studies, for the first time, provide mechanistic evidence that NOC induces apoptosis by the generation of reactive oxygen species and Akt dephosphorylation. Our findings highlight a new mechanism responsible for NOC-induced apoptosis, and raise the possibility that NOC might be promising as a candidate for human breast cancer therapy.

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Chrysin, a natural flavone, improves murine inflammatory bowel diseases

Cited by 100 publications

References 33 publications

Chrysin Ameliorates Chemically Induced Colitis in the Mouse through Modulation of a PXR/NF-κB Signaling Pathway

Chrysin Ameliorates Chemically Induced Colitis in the Mouse through Modulation of a PXR/NF-κB Signaling Pathway

Notoginsenoside R1 Attenuates Experimental Inflammatory Bowel Disease via Pregnane X Receptor Activation

Induction of apoptosis by 5,7-dihydroxy-8-nitrochrysin in breast cancer cells: The role of reactive oxygen species and Akt

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